The NIAID is seeking to develop assays for the improved early diagnosis of infectious diseases. In response, Physical Optics Corporation (POC) proposes to develop a novel Microfluidic Refractometric Biosensor (MRB) system based on fiber long-period Bragg grating (LPBG) optical probes, the tips of which are coated with a nanolayer gold mirror and positioned in a consecutively connected capillary array of a microfluidic chip. The MRB system will build upon POC's previously developed microfluidic refractometric proteomic array which has demonstrated high sensitivity to metalloproteinase in cancer related research. MRB system consists of three subsystems: (1) detection, (2) processing/analysis, and (3) microfluidic. The detection subsystem includes two pairs of the long period Bragg grating (LPBG) analyzing and reference probes coated with inhibitors of the Bacillus anthracis lethal factor or Botulinum neurotoxin; the processing/analysis subsystem consists of a laser diode, fiber optic cables, connectors, an optical switch, a coupler/beam splitter, and a high-precision optical spectrum analyzer feeding a microprocessor; the microfluidic subsystem combines a microfluidic chip with four channels/capillaries, injection and waste ports, a pump, and tubing with solenoid valves. The Phase I device prototype will perform label-free detection and concentration measurements of two metalloproteinases, anthrax lethal factor and botulinum neurotoxin, in unpurified samples of body fluids. In Phase I POC will design and fabricate an MRB model and demonstrate its sensitivity and selectivity. In Phase II the MRB will be optimized for diagnosis of infectious, allergen-caused, and immunologic diseases, culminating in the fabrication of a fully automatic, compact, durable, and highly sensitive device that will operate without labels. The proposed system will serve as a high-throughput detection platform for rapid recognition of infectious diseases based on protein-signature activity profiles. The system will accurately analyze multiple body fluid samples. Rapid functional proteomic analysis will facilitate early diagnosis, improve treatment, and speed the development of new drugs, all of which will contribute to public and individual health. [unreadable] [unreadable] [unreadable]